Kidney Dialysis Drug Diminishes HIV Bacteria From Leaving Gut.

Chronic activation of the immune system and inflammation are major determinants of progression of HIV infection to AIDS, and also play an important role in inducing excessive blood clotting and heart disease in HIV patients. Doctors believed this was due to microbial translocation, which occurs when bacteria in the gut gets out into the body through intestinal lining damaged by HIV. However, no direct proof of this mechanism existed.

Dr. Pandrea and her colleagues showed blocking the bacteria from leaving the intestine reduces the chronic immune activation and inflammation. They did this by giving the drug Sevelamer, also known by the brand names Renvela and Renagel, to monkeys newly infected with simian immunodeficiency virus, or SIV, the primate-form of HIV.

Sevelamer is an oral drug approved by the U.S. Food and Drug Administration to treat elevated levels of phosphate in the blood of patients with chronic kidney disease.

The gut bacteria bind to Sevelamer, making it much more difficult for the bacteria to escape into the body and cause serious problems, such as heart disease, while further weakening the immune system and allowing HIV to progress to full-blown AIDS.

In SIV-infected monkeys treated with Sevelamer, levels of a protein that indicates microbial translocation remained low. However, in the untreated monkeys the levels increased nearly four-fold a week after SIV infection.

The treated monkeys with the lower rates of microbial translocation also had lower levels of a biomarker associated with excessive blood clotting, showing that heart attacks and stroke in HIV patients are more likely associated with chronic immune system activation and inflammation, rather than HIV drugs.

"These findings clearly demonstrate that stopping bacteria from leaving the gut reduces the rates of many HIV comorbidities," said Dr. Pandrea.

Sevelamer is an oral drug approved by the U.S. Food and Drug Administration to treat elevated levels of phosphate in the blood of patients with chronic kidney disease.

The gut bacteria bind to Sevelamer, making it much more difficult for the bacteria to escape into the body and cause serious problems, such as heart disease, while further weakening the immune system and allowing HIV to progress to full-blown AIDS.

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I wonder if that is a safe drug that could be easily trialled on ME patients.

Health complications that often plague people living with HIV, and can prove fatal, might be reduced with the help of a drug already used to treat kidney disease – if it works as well in people as it does in monkeys.

The finding provides the first direct proof that microbes that leave the gut and travel to the rest of the body – a process called microbial translocation – is the mechanism that triggers these health complication in people with HIV.

Chronic activation of the immune system and inflammation are key triggers for the development of AIDS in many people with HIV, even if they are doing well on anti-retroviral drugs. That's because these immune responses in turn trigger a constellation of diseases normally associating with ageing, such as cardiovascular disease.

One hypothesis is that HIV damages the gut wall, allowing bacteria to leak out into the rest of the body, including the blood and other organs. Outside the gut, these bacteria prompt an inflammatory response that can lead to a cascade of other diseases.

Gut barrier
Earlier research found that people with HIV who had a leakier gut were more likely to die from these diseases. "Gut barrier integrity and immune activation predicts mortality; the leakier the gut, the sooner the patient dies," says Peter Hunt at the University of California, San Francisco, who conducted that research.

To find out whether microbial translocation is responsible, Ivona Pandrea at the University of Pittsburgh, Pennsylvania, and her colleagues gave a drug called sevelamer, every day for three months, to monkeys newly infected with the simian equivalent of HIV. Sevelamer is used to manage symptoms of chronic kidney disease, because it binds to unwanted phosphates in the gut, which the kidneys can no longer remove. But it can also bind to bacterial proteins, keeping them inside the gut where they can do no harm.

The team took blood samples from the monkeys at regular intervals to look for molecules that indicate activation of the immune system, as well as measuring the viral load of HIV, and compared these to a control group that did not receive the drug.

The researchers saw a dramatic reduction in systemic immune activation and inflammation, and a slight reduction in viral replication, in the group given sevelamer, compared to the control. "It suggests that early control of microbial translocation may improve the outcome of HIV infection and limit non-infectious [diseases] associated with AIDS such as cardiovascular disease," Pandrea says.

However, it may not be easy to get the same response in people.

No significant benefit
Four separate teams have tried different drugs including sevelamer to reduce microbial translocation and immune activation in humans, so far with no significant benefits, according to results presented at the Conference on Retroviruses and Opportunistic Infections which was held in Boston in March.

But Hunt thinks this may just be down to timing. The monkeys were treated early in the acute phase of their disease, soon after they were infected, whereas people in the studies had all been infected for many months or even years.

People infected with HIV have few signs of microbial translocation during the first six months of infection as it takes time for the virus to kill off epithelial cells and weaken the gut wall so that bacteria can leak through – so treating them early could be more effective.

Alternatively, a combination of treatments might work, Hunt says, possibly using a probiotic to modulate the gut microbiome, and an anti-inflammatory drug to dampen the immune response and problems associated with immune activation.

aids has many similarities with me/cfs, which i think most folk know. when i first got ill my doctor insisted that i have an hiv test due to a loss in weight. i knew it would be clear but the nurse said that i should bring a friend when i returned as what she saw in my mouth was exactly the same as she saw in hiv+ and chemo patients. a nurse understood my illness better than most doctors.

there has been at least one documented recovery from hiv+ i read of a few years ago. ive always felt that it can be cured, in a similar way to me/cfs, by mending the gut wall. meds, though, can't cure chronic conditions imo.